Cancer vaccines: progress reveals new complexities.

A decade ago, it seemed clear that our burgeoning knowledge of the molecular identities of tumor-associated antigens and a deeper understanding of basic immunology would point the way to an effective therapeutic cancer vaccine. Significant progress has been made and objective regressions after immune-based treatments are observed in some patients — even in those with bulky, metastatic disease. Notwithstanding this progress, we do not yet have a cancer vaccine in hand that can reliably increase patient survival or induce tumor destruction. The creation of therapeutic cancer vaccines has proven to be an enormous challenge, and many of the strategies learned in the development of highly successful vaccines against infectious agents simply do not apply to cancer vaccines. Issues of antigenic change and immune escape are present in both antitumor and antiviral situations. However, one big difference between antiviral and antitumor vaccines is that the former are preventative whereas the latter are generally expected to be therapeutic. Another problem with the targeting of tumor antigens relates to their poor immunogenicity. Tumor antigens appear to be relatively well tolerated in the host, perhaps because many of these antigens are also expressed in normal tissues. In this context, a successful cancer vaccine raises the specter of autoimmune attack if the vaccines are ultimately powerful enough to eliminate cancer cells. In this review, we highlight new challenges that have been revealed by recent progress in the field of tumor immunology. We then attempt to outline a future plan for cancer immunotherapy.